Neuroscience has long informed the development of artificial neural networks, but the success of modern architectures invites, in turn, the converse: can modern networks teach us lessons about brain function? Here, we examine the structure of the cortical column and propose that the transformer provides a natural computational analogy for multiple elements of cortical microcircuit organization. Rather than claiming a literal implementation of transformer equations in cortex, we develop a hypothetical mapping between transformer operations and laminar cortical features, using the analogy as an orienting framework for analysis and discussion. This mapping allows us to examine in greater depth how contextual selection, content routing, recurrent integration, and interlaminar transformations may be distributed across cortical circuitry. In doing so, we generate a broad set of predictions and experimentally testable hypotheses concerning laminar specialization, contextual modulation, dendritic integration, oscillatory coordination, and the effective connectivity of cortical columns. This proposal is intended as a structured hypothesis rather than a definitive account of cortical computation. Placing transformer operations and cortical architectonics into a common descriptive framework sharpens questions, reveals new functional correspondences, and opens a productive route for reciprocal exchange between systems neuroscience and modern AI. More broadly, this perspective suggests that comparing brains and architectures at the level of computational organization can yield genuine insight into both.
Alzheimer's disease (AD) is a complex neurodegenerative disorder characterized by the accumulation of amyloid-beta (A$β$) and phosphorylated tau (p-tau) proteins, leading to cognitive decline measured by the Alzheimer's Disease Assessment Scale (ADAS) score. In this study, we develop and analyze a system of ordinary differential equation models to describe the interactions between A$β$, p-tau, and ADAS score, providing a mechanistic understanding of disease progression. To ensure accurate model calibration, we employ Bayesian inference and Physics-Informed Neural Networks (PINNs) for parameter estimation based on Alzheimer's Disease Neuroimaging Initiative data. The data-driven Bayesian approach enables uncertainty quantification, improving confidence in model predictions, while the PINN framework leverages neural networks to capture complex dynamics directly from data. Furthermore, we implement an optimal control strategy to assess the efficacy of an anti-tau therapeutic intervention aimed at reducing p-tau levels and mitigating cognitive decline. Our data-driven solutions indicate that while optimal drug administration effectively decreases p-tau concentration, its impact on cognitive decline, as reflected in the ADAS score, remains limited. These findings suggest that targeting p-tau alone may not be sufficient for significant cognitive improvement, highlighting the need for multi-target therapeutic strategies. The integration of mechanistic modelling, advanced parameter estimation, and control-based therapeutic optimization provides a comprehensive framework for improving treatment strategies for AD.
Grahamstown's Assumption Convent was the first such institution to be established in Southern Africa. It was opened in January 1850 when in response to a request from Bishop Aidan Devereux, of the Eastern Cape, Mother Marie Eugenie, the founder of the Assumption Order in Paris, sent out a party under Sister Gertrude. The beginnings were simple: a small thatched cottage accommodated the sisters while a free school, St Joseph's, was started in two convened stables. A fee-paying school, St Catherine's, was also established. Gradually the sisters involved themselves not only in education but also in all facets of communal work. Their contribution in many ways has been of inestimable value and although the Assumption Convent in Grahamstown closed down at the end of 1982 the Sisters continue to work in Grahamstown and in other centres among the young, the needy, the aged, and the infirm.
Functional Connectivity between brain regions is known to be altered in Alzheimer's disease, and promises to be a biomarker for early diagnosis of the disease. While several approaches for functional connectivity obtain an un-directed network representing stochastic associations (correlations) between brain regions, association does not necessarily imply causation. In contrast, Causal Functional Connectivity is more informative, providing a directed network representing causal relationships between brain regions. In this paper, we obtained the causal functional connectome for the whole brain from recordings of resting-state functional magnetic resonance imaging (rs-fMRI) for subjects from three clinical groups: cognitively normal, mild cognitive impairment, and Alzheimer's disease. We applied the recently developed Time-aware PC (TPC) algorithm to infer the causal functional connectome for the whole brain. TPC supports model-free estimation of whole brain causal functional connectivity based on directed graphical modeling in a time series setting. We then perform an exploratory analysis to identify the causal brain connections between brain regions which have altered strengths between pairs of subject groups, and over the three subject groups, based on edge-wise p-values from statistical tests. We used the altered causal brain connections thus obtained to compile a comprehensive list of brain regions impacted by Alzheimer's disease according to the current data set. The brain regions thus identified are found to be in agreement with literature on brain regions impacted by Alzheimer's disease, published by researchers from clinical/medical institutions.
In this paper, we define a matrix over neutrosophic components (NCs), which was built using the four different intervals (0,1), [0,1), (0,1], and [0,1]. This definition was made clear by introducing some examples. Then, the study of the algebraic structure of matrices over NC under addition modulo 1, the usual product, and product by using addition modulo 1 was introduced, from which it was found that the matrix over NC built using interval [0,1) happens to be an abelian group under addition modulo 1. Furthermore, it is proved that the matrix over NC defined on the interval [0,1) is not a regular semiring. Also, we define a matrix over multiset NC semigroup using the interval [0,1). Moreover, we define a matrix over m‐multiplicity multiset NC semigroup for finite m. Several interesting properties are discussed for the three structures. It was concluded that the last two structures are semigroups and semirings under addition modulo 1 and usual product, respectively.
Neural mass models are used to simulate cortical dynamics and to explain the electrical and magnetic fields measured using electro- and magnetoencephalography. Simulations evince a complex phase-space structure for these kinds of models; including stationary points and limit cycles and the possibility for bifurcations and transitions among different modes of activity. This complexity allows neural mass models to describe the itinerant features of brain dynamics. However, expressive, nonlinear neural mass models are often difficult to fit to empirical data without additional simplifying assumptions: e.g., that the system can be modelled as linear perturbations around a fixed point. In this study we offer a mathematical analysis of neural mass models, specifically the canonical microcircuit model, providing analytical solutions describing dynamical itinerancy. We derive a perturbation analysis up to second order of the phase flow, together with adiabatic approximations. This allows us to describe amplitude modulations as gradient flows on a potential function of intrinsic connectivity. These results provide analytic proof-of-principle for the existence of semi-stable states of cortical dynamics at the scale of a cortical column. Crucially, this work allows for model inversion of neural mass models, not only around fixed points, but over regions of phase space that encompass transitions among semi or multi-stable states of oscillatory activity. In principle, this formulation of cortical dynamics may improve our understanding of the itinerancy that underwrites measures of cortical activity (through EEG or MEG). Crucially, these theoretical results speak to model inversion in the context of multiple semi-stable brain states, such as onset of seizure activity in epilepsy or beta bursts in Parkinsons disease.
Jonas Benhamou, Michel Le Van Quyen, Guillaume Marrelec
Objective. In neuroscience, time-frequency analysis has been used to get insight into brain rhythms from brain recordings. In event-related protocols, one applies it to investigate how the brain responds to a stimulation repeated over many trials. In this framework, three measures have been considered: the amplitude of the transform for each single trial averaged across trials, avgAMP; inter-trial phase coherence, ITC; and the power of the evoked potential transform, POWavg. These three measures are sensitive to different aspects of event-related responses, ITC and POWavg sharing a common sensitivity to phase resetting phenomena. Methods. In the present manuscript, we further investigated the connection between ITC and POWavg using theoretical calculations, a simulation study and analysis of experimental data. Results. We derived exact expressions for the relationship between POWavg and ITC in the particular case of the S-transform of an oscillatory signal. In the more general case, we showed that POWavg and ITC are connected through a relationship that roughly reads $\mathrm{POWavg} \approx \mathrm{avgAMP}^2 \times \mathrm{ITC}^2$. This result was confirmed on simulations. We finally compared the theoretical prediction with results from real data. Conclusion. We showed that POWavg and ITC are related through an approximate, simple relationship that also involves avgAMP. Significance. The presented relationship between POWavg, ITC, and avgAMP confirms previous empirical evidence and provides a novel perspective to investigate evoked brain rhythms. It may provide a significant refinement to the neuroscientific toolbox for studying evoked oscillations.
Bhanu Sharma, Spandan Kumar, Subhendu Ghosh
et al.
In the brain, both neurons and glial cells work in conjunction with each other during information processing. Stimulation of neurons can cause calcium oscillations in astrocytes which in turn can affect neuronal calcium dynamics. The "glissandi" effect is one such phenomenon, associated with a decrease in infraslow fluctuations, in which synchronized calcium oscillations propagate as a wave in hundreds of astrocytes. Nitric oxide molecules released from the astrocytes contribute to synaptic functions on the basis of the underlying astrocyte-neuron interaction network. In this study, by defining an astrocyte-neuronal (A-N) unit as an integrated circuit of one neuron and one astrocyte, we developed a minimal model of neuronal stimulus-dependent and nitric oxide-mediated emergence of calcium waves in astrocytes. Incorporating inter-unit communication via nitric oxide molecules, a coupled network of 1,000 such A-N units is developed in which multiple stable regimes were found to emerge in astrocytes. We examined the ranges of neuronal stimulus strength and the coupling strength between A-N units that give rise to such dynamical behaviors. We also report that there exists a range of coupling strength, wherein units not receiving stimulus also start showing oscillations and become synchronized. Our results support the hypothesis that glissandi-like phenomena exhibiting synchronized calcium oscillations in astrocytes help in efficient synaptic transmission by reducing the energy demand of the process.
David Rudrauf, Grégoire Sergeant-Perthuis, Yvain Tisserand
et al.
Relating explicit psychological mechanisms and observable behaviours is a central aim of psychological and behavioural science. We implemented the principles of the Projective Consciousness Model into artificial agents embodied as virtual humans, as a proof-of-concept for a methodological framework aimed at simulating behaviours and assessing underlying psychological parameters, in the context of experiments in virtual reality. We focus on simulating the role of Theory of Mind (ToM) in the choice of strategic behaviours of approach and avoidance to optimise the satisfaction of agents' preferences. We designed an experiment in a virtual environment that could be used with real humans, allowing us to classify behaviours as a function of order of ToM, up to the second order. We show that our agents demonstrate expected behaviours with consistent parameters of ToM in this experiment. We also show that the agents can be used to estimate correctly each other order of ToM. A similar approach could be used with real humans in virtual reality experiments not only to enable human participants to interact with parametric, virtual humans as stimuli, but also as a mean of inference to derive model-based psychological assessments of the participants.
Peter A. V. DiBerardino, Alexandre L. S. Filipowicz, James Danckert
et al.
Prior beliefs are central to Bayesian accounts of cognition, but many of these accounts do not directly measure priors. More specifically, initial states of belief heavily influence how new information is assumed to be utilized when updating a particular model. Despite this, prior and posterior beliefs are either inferred from sequential participant actions or elicited through impoverished means. We had participants play a version of the game "Plinko", to first elicit individual participant priors in a theoretically agnostic manner. Subsequent learning and updating of participant beliefs was then directly measured. We show that participants hold a variety of priors that cluster around prototypical probability distributions that in turn influence learning. In follow-up experiments we show that participant priors are stable over time and that the ability to update beliefs is influenced by a simple environmental manipulation (i.e. a short break). This data reveals the importance of directly measuring participant beliefs rather than assuming or inferring them as has been widely done in the literature to date. The Plinko game provides a flexible and fecund means for examining statistical learning and mental model updating.
Representation of brain network interactions is fundamental to the translation of neural structure to brain function. As such, methodologies for mapping neural interactions into structural models, i.e., inference of functional connectome from neural recordings, are key for the study of brain networks. While multiple approaches have been proposed for functional connectomics based on statistical associations between neural activity, association does not necessarily incorporate causation. Additional approaches have been proposed to incorporate aspects of causality to turn functional connectomes into causal functional connectomes, however, these methodologies typically focus on specific aspects of causality. This warrants a systematic statistical framework for causal functional connectomics that defines the foundations of common aspects of causality. Such a framework can assist in contrasting existing approaches and to guide development of further causal methodologies. In this work, we develop such a statistical guide. In particular, we consolidate the notions of associations and representations of neural interaction, i.e., types of neural connectomics, and then describe causal modeling in the statistics literature. We particularly focus on the introduction of directed Markov graphical models as a framework through which we define the Directed Markov Property -- an essential criterion for examining the causality of proposed functional connectomes. We demonstrate how based on these notions, a comparative study of several existing approaches for finding causal functional connectivity from neural activity can be conducted. We proceed by providing an outlook ahead regarding the additional properties that future approaches could include to thoroughly address causality.
Ignacio Cifre, Maria T. Miller Flores, Jeremi K. Ochab
et al.
The center stage of neuro-imaging is currently occupied by studies of functional correlations between brain regions. These correlations define the brain functional networks, which are the most frequently used framework to represent and interpret a variety of experimental findings. In previous work we first demonstrated that the relatively stronger BOLD activations contain most of the information relevant to understand functional connectivity and subsequent work confirmed that a large compression of the original signals can be obtained without significant loss of information. In this work we revisit the correlation properties of these epochs to define a measure of nonlinear dynamic directed functional connectivity (nldFC) across regions of interest. We show that the proposed metric provides at once, without extensive numerical complications, directed information of the functional correlations, as well as a measure of temporal lags across regions, overall offering a different perspective in the analysis of brain co-activation patterns. In this paper we provide for a proof of concept, based on replicating and completing existing results on an Autism database, to discuss the main features and advantages of the proposed strategy for the study of brain functional correlations. These results show new interpretations of the correlations found on this sample.
Ruben Sanchez-Romero, Joseph D. Ramsey, Kun Zhang
et al.
Standard fMRI connectivity analyses depend on aggregating the time series of individual voxels within regions of interest (ROIs). In certain cases, this spatial aggregation implies a loss of valuable functional and anatomical information about smaller subsets of voxels that drive the ROI level connectivity. We use two recently published graphical search methods to identify subsets of voxels that are highly responsible for the connectivity between larger ROIs. To illustrate the procedure, we apply both methods to longitudinal high-resolution resting state fMRI data from regions in the medial temporal lobe from a single individual. Both methods recovered similar subsets of voxels within larger ROIs of entorhinal cortex and hippocampus subfields that also show spatial consistency across different scanning sessions and across hemispheres. In contrast to standard functional connectivity methods, both algorithms applied here are robust against false positive connections produced by common causes and indirect paths (in contrast to Pearson's correlation) and common effect conditioning (in contrast to partial correlation based approaches). These algorithms allow for identification of subregions of voxels driving the connectivity between regions of interest, recovering valuable anatomical and functional information that is lost when ROIs are aggregated. Both methods are specially suited for voxelwise connectivity research, given their running times and scalability to big data problems.
Neuronal responses to complex stimuli and tasks can encompass a wide range of time scales. Understanding these responses requires measures that characterize how the information on these response patterns are represented across multiple temporal resolutions. In this paper we propose a metric -- which we call multiscale relevance (MSR) -- to capture the dynamical variability of the activity of single neurons across different time scales. The MSR is a non-parametric, fully featureless indicator in that it uses only the time stamps of the firing activity without resorting to any a priori covariate or invoking any specific structure in the tuning curve for neural activity. When applied to neural data from the mEC and from the ADn and PoS regions of freely-behaving rodents, we found that neurons having low MSR tend to have low mutual information and low firing sparsity across the correlates that are believed to be encoded by the region of the brain where the recordings were made. In addition, neurons with high MSR contain significant information on spatial navigation and allow to decode spatial position or head direction as efficiently as those neurons whose firing activity has high mutual information with the covariate to be decoded and significantly better than the set of neurons with high local variations in their interspike intervals. Given these results, we propose that the MSR can be used as a measure to rank and select neurons for their information content without the need to appeal to any a priori covariate.